COMMUNICATIONS TO THE EDITOR
Sept. 5 , 1960
concerning a possible role for Qlo in oxidative phosphorylation mechanisms; also, concerning analyses for vitamin E, since the chromanol I1 is a methoxy analog of vitamin E. However, the natural occurrence of the chromanol I1 has not yet been established.
4745
TABLE I PROPERTIESOF ELECTRON SPIN RESONANCE SPECTRAOF SEMIQUINONES OBTAINED BY OXIDATION O F 2,fI-DI-TERTBUTYL-4-R PHENOL R
Approx. i n t . ratios of hyperfine lines
Coupling constants, gauss 01
0 2
LMethyl 1:1:3:3:3:3:1:1 5.2 2.5 1:1:2:2:1:1 4 1 2 5 Benzyl" Isopropyl" 1:2 : 1 2 4 2 4 2.5 tert-Butyl 1: 1 Provided by the courtesy of Dr F. C. Davis and Dr. G. C. Coppinger of Shell Development Company.
CONTRIBUTION FROM THE MERCKSHARP & DOHME CARLH. HOFFMAN RESEARCH LABORATORIES NELSONR . TRENNER DIVISIONO F MERCK& CO., INC. DONALDE. WOLF SEW JERSEY KARLFOLKERS RAHWAY, RECEIVED JULY 11, 1960
R
R
If I (R = CH3) is allowed to decompose in alkaline solution, the characteristic e.s.r. spectrum of the corresponding semiquinone appeass in about four hours. If an equimolar solution of I and I11 (R = CH3) or an equimolar solution of cumene hydroperoxide and 11 is made alkaline, a strong e.s.r. spectrum appears immediately. Gersmann and Bicke12 have suggested that an orthoquinone formed by the decomposition of IV may be responsible for the autocatalytic behavior of the main oxidation reaction. The present work indicates that orthoquinones almost certainly are produced. The mechanism of the olefin elimination reaction giving rise to the orthosemiquinones and orthoquinones is obscure. It is probably significant that the product is an orthosemiquinone rather than a parasemiquinone even if R = t-butyl. Acknowledgment.-It is a pleasure to acknowledge helpful discussions with staff members of this laboratory and particularly with Dr. S. I. Weissman of Washington University and Dr. G. &I. Coppinger of Shell Development Company.
I11
Iv
WOOD
OXIDATION OF HINDERED PHENOLS T O SEMIQUINONES
Sir: The reactions between oxygen and hindered phenols in alkaline solution have been reported in several recent paper^.'^^^^^^ The major products a t low temperatures are peroxides of structure I which in alkaline solution can decompose1n2 to I1 or 111 or rearrange to IV. Free radicals whose 0
0
I-Bu
i-Bu&
~-B~&,-B~
iii'
R
52
OOH
OH
R
I
I1
OH
0 i-Bu
i-Bu
structure has not been explained heretofore have been ~ b s e r v e d in ~ , ~this system by electron spin resonance (e.s. r .) spectroscopy. We wish to report an unusual new reaction, isobutene elimination leading to the formation of pyrocatechol semiquinones V which are responsible for the observed e s r . spectra (Table I).
RIVERRESEARCH LABORATORY
SHELL OILCOMPANY
J. J. CONRADI WOODRIVER,ILLINOIS G A. MCLAREN RECEIVED MAY31, 1960
OPTICALLY ACTIVE 0%. VINYL 11D . THE o p T I c A L ~kCTIVITy ~ I S POLYMERS. OTAcTIc~A~ POLYMERS OF OPTICALLY ACTIVE a-OLEFINS DILUTE HYDROCARBON SOLUTION
IN
Sir: Although the existence of spiralized sonformations of the macromolecules of many vinyl polymers in the solid state has been recognized since tBL1+O-I1 1954,l no experimental evidence for the existence of such types of conformations in the liquid phase V has been reported. The isobutene evolved has been identified by gasThe data given here seem to support the hyliquid chromatography and mass spectrometry. pothesis that, in the case of poly-cu-olefins, helical Two of the suspected pyrocatechols, 3-tert-butyl-5- conformations can exist above the melting point methylpyrocatechol and 3,5-di-tert-butylpyrocate- and in dilute solution.2 chol, have been prepared. The e.s.r. spectra of the we have reported recently, the crystalline semiquinones of these two compounds are identical isotactic and block polymers of (+) (S)-3-methyl-lwith the spectra observed on oxidation 2,6-di(1) G. N a t t a a n d co-workers, S u o v o Cimento, [XI, Suppl. 15, 1-168 tert-butyl-4-methylphenol and 2,4,6-tri-tert-butyl- (1960). ( 2 ) G. K a t t a , et al. (private communication) have obtained some phenol, respectively. evidence for t h e existence of helical conformations of poly-wolefins in A
(1) M. S. Kharasch a n d B . S. Joshi, J. Org. Chem., 28, 1439 (1957). (2) H. R . Gersmann a n d A . F. Bickel, J . Chem. SOL.,2711 (1959). (3) G . G. Yohe, e t al., J . Ovg. Chem., 24, 1251 (1959). (4) A. Fairbourn a n d E . A. C . Lucken, PYOC. Chem. SOL.,67 (1950). (5) M. Adams, M. S. Blois, and R . H. Sands, J . Chem. P h y s . , 26, 774 (1958). (6) J. K . Becconsall, S. Clough, a n d Gerald S c o t t , PYOC. Chem. SOL., 30E (1959).
%
~
solution from infrared spectra. Similar evidence h a s been obtained by H. Tadokoro, S. hTozakura, T. Kitazawa, Y. Yasuhura a n d S . M u r a hashi, (Bull. Chem. SOC.J a p a n , 31, 813-316 (1958)) (3) P. Pino, G. P. Lorenzi and L. Lardicci, a b s t r a c t s of papers of Symposium for Macromolecular Chemistry, Moskow, 14-18, June, 1960. Communication t o t h e Italian Chemical Society Meeting held in Florence on April 2nd, 1960, Chimica e Industvia, 42, in press (1960).
4746,
Vol. 82
COMMUNICATIONS TO THE EDITOR TABLE I
M E L T I N G POINT, IXTRINSIC vISCOSITY AND SPECIFIC ROTATION OF DIFFERENT FRACTIOSS O F POLY-( S)-3-METHYL-l-PENTESE Solvent used for the Fraction extractiona
1 2' 3
6.3
...
2.6 0.9 0.4 2.7 87.lf
65-75 135-140 175-180 228-232 271-2738
4 5 6e ... A t t h e solvent boiling point.
d
0.08 i 0.01 0.09i 0.01 0.09 0 . 0 1 0 . 8 i 0.1
*
...
+35,5 i0.5 +124 zt 2
1 .9% 0.702
+145 =k 2
0,080 0.018
Bz Bz Bz Bz
0.023
Dec.
...
...
+190 i 10 +191 i 10 ...
Based on t h e crude polymer. Determined using a Kofler m.p. apparatus. Mol. wt. determined by cryoscopy in benzene, 1200. e The fraction shows crystallinity a t the X-ray esaminatiun. Residue. Determined by the capillary method. a
'
.Acetone Diethyl ether Isooctane Benzene Decalin
TABLE I1
ROTATIONS OF
PARTIALLY CRYSTALLISE POLY-(S)-5-METHYL-1-HEPTESEI N THE SOLID ASL)
LIQUII)STATE A S D
IS
DECALIX
SOLUTION AT DIFFERENT TEMPERATURES
+
aD
Solid, partially crystalline polymer" 1.02 Melted polymer $0.96 Decalin solution +0.95b M.p. determined by X-ray and Kofier methods:
I , dm.
0.02
0.02 1.00 48-52'.
pentene, (-) (S)-4-methyl-l-hexene and (+) (S)5-methyl-1-heptene dissolved in hydrocarbon solvents, show molar optical rotation, referred to the monomeric unit, of magnitudes 5 t o 25 times greater than the molar optical activity of low molecular weight parafines, whose structures closely resemble the structure of the monomeric units of the considered polymers. By fractionation of the crude poly-(S)-3-methyl1-pentene with different solvents, fractions having different melting points (i.e., different stereoregularity) and different optical activities have been obtained, the specific rotations increasing with increasing stereoregularity (Table I). The same behavior has been observed for the poly-(S)-4-methyl-l-hexene (acetone extract [arIz0D +104'; ether extract [ a I 2 ' D +26x0; isooctane extract [ a ] " ~+27s0) and for poly-(S)-% methyl- 1-heptene (acetone extract [ LY ]"OD 3.7 ; ether extract [ a ] % $60"). The rotation o f thc ~ ~ 0 1 ~ ~ - ( S j - ~ - l 1n-1ieptcne cthylinsoluble in acetoiie and showing crystallinity o n X-ray exaniination, has been nieasured (a) a t room temperature, (b) above the melting point, aiid (c) in dilute decalin solution at different t e n peratures. ,Is is show11 in Table 11, the specific rotation in the solid state and in solution at room temperature are about the same, but the temperature coefficients of the rotation are very different, being very small for the pure polymer below its melting point, but remarkably high for both the molten polymer and for the solution. The observed temperature depending xrariations of the rotatory power are completely reversible.
+
(-1) T h e fractions ieported in T a b l e I are different not only in stereoregularity b u t also in molecular weight: therefore t h e possible influence of t h e molecular weight on optical rotation should be in principle considered. T a k i n g i n account t h e results of hl. Goodman and E. Schmitt I T H I S J O U R N A L , 81, .j.XlS (lU.59)] for t h e p o l y - y methyl-L-glutamate and considering t h a t t h e acetone strluble fraction of poly-(S)-3-methyl-l-i,entenehas a number average mol. u t . of 1200 corresponding t o a b o u t 14 monnmeric units, a v r r y remarkable effect of mol. nt. on optical rotation s h o d d be excluded.
c. [QID 19.0 S59.6 56.0 ... 18.5 +56.5 'r c = 1.69 t,
l a D \ l = I)/
Alaju'
AI
Ai
O
-0.04 -0.30
...
-0.01
're ni p , interval, O C .
cn.
... - 0 . 53
19.0-44.5 56.0-105.0 18.k96.5
The high value found for the molar optical rotation of the optically active poly-a-olefins, the increase of the optical rotation with their stereoregularity and the value of the temperature coefficient of their optical rotation in solution, which is much higher than the coefficient found for the low molecular weight paraffins and of the same order of magnitude of some spiralized proteins (Table 111) and of the poly-L-glutamic acid,j clearly show that the optical rotation in the polya-olefins does not arise solely from the existence of asymmetric carbon atoms in the lateral chains. TABLE 111 TEMPERATURE COEFFICIENTS OF THE OPTICALROTATIUS OF SOME LOR'
?dOLECULAR \\-EIGHT PARAFFINS, O F POLY-aOLEFISS AND OF SILKFIBROIS A [ ID: Temp. [ . I D 1, "C. interval. ' C .
(s)-3-irctilyihexane" (3s:6S)-3,G-L)imethyloctane"
-+ +
S.78 16.8,j
l.?.O-O.OO'J
1-5.(J-71.0
13.0
.ill2 Sf.t~-115.T,
lS.O
.Mi
l'oly-(S)-4-tnet liyl-
l-Iiexeneh $286 Poly-(S)-5-metllyl1-hcptenc" -/- 5 G . 5 Silk fibroin,' 43
18.0-07..7
18.5 .2.? 18.5-96.3 14 .3 14-41 a D. Hardiii and S. Sikorsk)-, J . Chilit. I'hys., 6, 179 (1908). Isooctane estract in tetralin solution. Ether
+
estract in decalin solution. In 1 : 4 dichloroacetic acidethylene dichloride mixture; J. T. P a n g and P. Doty, THISJOURNAL, 79, 761 (1957).
ils the poly-a-olefins we have examined are isotactic or stereoblock polymers, the high optical rotation cannot be ascribed t o the asymmetric carbon atoms of the principal chains of the macromolecules. I n order t o explain the high optical rotation and its remarkable dependence on stereoregularity and ( 5 ) P. D o t y , A. W a d a , J. 1 . . Yang and E. 11. Blout, J. Polymer Sci., 23, 851 (1957).
Sept. 5, 1960
COMMUNICATIONS TO THE EDITOR
temperature,6 we suggest that in dilute solution and in the molten state the isotactic and block polymers of optically active a-olefins are a t least in part spiralized and that helices of a single screw sense largely prevail. ( G ) For t h e highly stereoregular fractions of poly-(S)-3-methyl-lpentene which have a very low solubility and high melting point it is possible t h a t t h e solutions of t h e polymers still cuntain crystalline molecular aggregates which undergo dissociation b y increasing t h e temperature. I n this case, t h e decrease of t h e optical activity b y increasing t h e temperature, could be a t t r i b u t e d t o t h e dissociation of t h e crystalline aggregates ha\.ing high optical activity t o dissolved less optically active macromolecules, which may change or eventuall) loose their spiralized conformation. G. S a t t a . RI. F a r i n a , RI. Peraldo, P. Corradini, G. Bressan a n d P. Ganis (Reird. Acc. h ' n s . L i n c e i , April, 1960) have found crystalline molecular aggregates in solutions of some di-isotactic polymers. W e are particularly indebted t o Prof. N a t t a a n d his co-workers for t h e discussion on this point. ISTITUTO D I CHIMICA ORGASICA ISDUSTRIALE UNIVERSITA DI PISA
VIA RISORGIMENTO 19 PISA,ITALY RECEIVED JUNE 4, 1960
P.P I N 0 G. P. LORENZI
4747
III'O and the hitherto unknown amino acid IV designated by us as thiostreptoic acid. NH2 S-CH I I I/ CHZ-CH-Cb /C-COOH
S-CH I I R-C+ /C-COOH
h'
i
N I, R = CH2NH2 11,R CH&H*CHNH, 111,R=CH,CH:CO
CH,-CH-W I
I
N 'C-COOH
NH: S-iH
IV S-CH
CH?-CO-Cb
I
I1
/C-COOH
N N\C-COOH CH9-CO-CP I I/
I
S-CH
v
The crystalline acid IV was isolated from the hydrolysate after removal of impurities by butanol DEGRADATION OF THIOSTREPTON. extraction. The dihydrate melts a t 235-237" THIOSTREPTOIC ACID (dec.); * O (c, 1.0 in 1 N HC1); XitxHc' Sir: 236 rnp ( e = 15,000); Anal. weight loss a t 110": Earlier publications from this Laboratory have 9.7; calcd. for 2 H 2 0 : 9.5; calcd. for C12H1404N4S2: described the isolation and characterization1 as C, 42.1; H , 4.12; N , 16.4; S, 18.17. Found: C, well as the biological proper tie^^,^ of the antibiotic 42.3; H, 4.21; N , 16.4; S, 18.6. On Whatman thiostrepton. Kenner, et u Z . , ~ have isolated the No. 1 paper in a system of 1-butanol-acetic acid4-thiazolecarboxylic acids I and I1 from acid hy- water (4 : 1: 1) thiostreptoic acid moves somewhat drolysates of the antibiotic. This Communication faster than cystine, Rf = 0.08-0.10. In 1 N presents our own degradative studies with thio- HCl it forms a crystalline dihydrochloride, which, strep-ton. when dissolved in water, deposits the free acid. Separation of water-soluble components of acid Treatment of IV in water with acetic anhydride in hydrolysates (6 NHC1,lG hours a t 105') by counter- the presence of triethylamine yields the correspondcurrent distribution, then partition chromatog- ing N,N'-diacetyl derivative, m.p. 275-277' (dec.). raphy, led to the isolation of L-threonine, L- Anal. Weight loss a t l l O a , 10.4; calcd. for 3 H20: isoleucine, L-alanine, and of c cystine.^ The iden - 11.2; calcd. for C16H1806N4S2: c, 45.3; H, 4.26; s, tity of these components was ascertained by com- 15.1. Found: C,45.3; H,4.38; S,l5.l. Onbotha parison with authentic samples on paper chromato- reaction with dinitrofluorobenzene I V forms monograms, by infrared spectra and by measurement of and bis-dinitrophenyl derivative." The former their optical rotation. No other conventional amino is ninhydrin positive. From the specific absorpacids were found. From a partial hydrolysate tion of the monodinitrophenyl derivative a t 35,5 (6 N HCI a t room temperature) L-isoleucyl-L- mp a molecular weight of about 500 was calculated. alanine6 was obtained in crystalline form and iden- Titration of monodinitrophenylthiostreptoic acid tified by paper chromatographic separation of the with alkali and acid gave neutralization equivacomponents liberated by hydrolysis before and lents of 2 5 i and 539, respectively (mol. wt., 508). after dinitrophen ylation. Reduction of IV with sodium in liquid ammonia Hydrolysis of thiostrepton with a 1:1 mixture and then acid hydrolysis12 led to a mixture, in of concentrated hydrochloric and formic acids7 which alanine and cystine were identified by paper furnished in addition to the previously isolated4 chromatography. Oxidation of thiostreptoic acid thiazolecarboxylic acidss I and IT,9the keto acid (8) T h e fact t h a t acid hydrolysis of t h e product obtained from t h i o (1) J. V a n d e p u t t e a n d J . D. Dutcher, "Antibiotics Annual, 19551Y56," Medical Encyclopedia, Inc., New York. N. Y., p . 5 6 0 . (2) J . F. Pagano, M. J . Weinstein, H . A. S t o u t a n d R. Donovick, i b i d . , 1955-1950, p . 554. ( 3 ) B . A. Steinberg, a '. P. Jambor a n d L y d a 0. S u y d a m , i b i d . , 19551956, p . 5 6 2 . ( 4 ) G. W. Kenner, R. C. Sheppard a n d C. E. Stehr, Tcbohcdron Lclfcrs, 23 (1960). (5) I n thiostrepton this D-amino acid occurs in t h e reduced form, a s shown b y t h e absence of a reaction for disulfides in t h e antibiotic a n d t h e positive test for sulfhydryl after hydrolysis. Moreover, t h e behavior of this amino acid during fractionation b y countercurrent distribution or b y partition chromatography was characteristic of cysteine r a t h e r t h a n cystine. (6) Isoleucine a n d alanine were also found in a diketopiperazine formed during pyrolysis of t h e antibiotic a t 250' i n vacuo. (7) G .L. Miller and V. du Vigneaud, J. B i d . Chcm., 118, 101 (1937).
strepton b y reduction with sodium in liquid ammonia yields glycine a n d a-aminohutyric acid indicates t h a t t h e thiazolecarboxylic acids I a n d 11, a n d probably also IV, are present a s such in t h e parent molecule a n d n o t , for instance, as thiazolines. (9) I n these studies, I 1 was isolated a s a crystalline salt with Phydroxyaeohenzene-p'sulfonic acid. Anal. Calcd. for CioHmOaS&: C,49.1; H , 4.34; S, 13.8. Found: C, 48.9; H, 4.46; S, 13.7. ( I O ) T h e acid 111,probably formed a s a secondaly degradation produ c t from 11, was f o u n d t o be identical with t h e acid isolated b y P. Brookes, A. T. Fuller and J . Walker (J. Chem. Sac., 689 (1957)) from Micrococcin P . A homologous keto acid was reported a s a secondary degradation product f r o m bacitracin A (J. R. Weisiger, W. H a u s m a n n a n d L. C. Craig, THISJOURNAL, 17, 3123 119551). (11) A. R. Battershy a n d L. C. Craig, THIS JOURNAL, 1 3 , 1887 (1951); 74, 4023 (1952). (12) P. Brookes, R . J. Clark, B. Majhofer, M. P. V. Mijovic and J. LX'alker, J. Chevi. S o c . , 925 (IQCO).
